title: Effect of DDVP on urinary excretion levels of pyrethroid metabolite 3-phenoxybenzoic acid in rats.
abstract: Pyrethroid insecticide (PYR) is used worldwide in agriculture and for indoor extermination of harmful insects. Urinary PYR metabolites (e.g. 3-phenoxybenzoic acid, 3PBA) have been used as the most sensitive biomarker for environmental PYR exposure since the late 1990s. In this study, we examined the effect of organophosphorus insecticide (OP) dichlorvos (DDVP) on excretion levels of urinary cis-permethrin-derived 3PBA in rats. Concentration of urinary 3PBA and cis-permethrin in plasma was monitored using gas chromatography-mass spectrometry and high-performance liquid chromatography after cis-permethrin injection (20 mg/kg) via the tail vein of rats pretreated intraperitoneally with DDVP (low dose, 0.3 mg/kg; high dose, 1.5 mg/kg). The amount of urinary 3PBA excretion over 48 h after cis-permethrin administration in control was 21.5±5.1 μg (mean±S.D.). In the low- and high-dose DDVP groups, the amounts of urinary 3PBA excretion were decreased to 81.1% (17.4±2.7 μg) and 70.3% (15.1±2.6 μg) of control, respectively. The plasma concentrations of cis-permethrin-derived 3-phenoxybenzyl alcohol (3PBAlc), which is a metabolite derived following hydrolysis of cis-permethrin, in high-dose DDVP group (0.18±0.01 μg) were significantly lower than in control (0.23±0.03 μg) 1h after cis-permethrin injection. Both in the control and high-dose DDVP group, no differences were observed in the excretion levels of urinary 3PBA after injection of 3PBAlc (25mg/kg, i.v.). These results suggested that the effect of DDVP on the amount of urinary 3PBA excretion was caused by the DDVP-induced modification of the cis-permethrin metabolic pathway. In conclusion, the possible decrease in urinary excretion level of 3PBA due to co-exposure to OPs should be considered in the biological monitoring of PYR exposure.
authors.affiliation: Department of Pathophysiological Laboratory Sciences, Nagoya University Graduate School of Medicine, Nagoya 461-8673, Japan.
authors.forename: Naoko
authors.initials: N
authors.lastname: Hirosawa
authors.forename: Jun
authors.initials: J
authors.lastname: Ueyama
authors.forename: Takaaki
authors.initials: T
authors.lastname: Kondo
authors.forename: Michihiro
authors.initials: M
authors.lastname: Kamijima
authors.forename: Kenji
authors.initials: K
authors.lastname: Takagi
authors.forename: Sanae
authors.initials: S
authors.lastname: Fujinaka
authors.forename: Ayaka
authors.initials: A
authors.lastname: Hirate
authors.forename: Takaaki
authors.initials: T
authors.lastname: Hasegawa
authors.forename: Shinya
authors.initials: S
authors.lastname: Wakusawa
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001565:Benzoates / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity / Q000652:urine*; D001592:Benzyl Alcohols / Q000008:administration & dosage / Q000097:blood; D015415:Biomarkers / Q000652:urine; D001711:Biotransformation; D002091:Butyrylcholinesterase / Q000378:metabolism; D043182:Carboxylesterase / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004006:Dichlorvos / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity / Q000652:urine*; D004784:Environmental Monitoring / Q000379:methods; D008401:Gas Chromatography-Mass Spectrometry; D007274:Injections, Intraperitoneal; D007275:Injections, Intravenous; D007306:Insecticides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics / Q000633:toxicity / Q000652:urine*; D008297:Male; D008954:Models, Biological; D026023:Permethrin / Q000652:urine; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001565:Benzoates; D001592:Benzyl Alcohols; D015415:Biomarkers; D007306:Insecticides; C064809:3-phenoxybenzylalcohol; D026023:Permethrin; C017618:3-phenoxybenzoic acid; D004006:Dichlorvos; D043182:Carboxylesterase; D002091:Butyrylcholinesterase